It is likely that the activity of excitable membranes such as those of heart and nerve can be strongly influenced by molecular interactions between permeability mediating membrane components ("channels") and the lipid matrix of the supporting bilayer membrane. This study is designed to elucidate the molecular mechanisms by which the internal or surface composition of the lipid bilayer may alter the magnitude, kinetics and selectivity of ion transport. Membrane-channel interactions will be assessed by monitoring ion permeability induced by simple, peptide-like molecules of known structure that form conductive pores spanning the bilayer membrane. The lipid composition of the membrane will be taylored to approximate that of excitable cell membranes. This will be achieved not only by using novel techniques, developed in our laboratory for the formation of solventless planar bilayers but also by forming bilayers from either synthetic or naturally occurring lipids whose hydrocarbon tails (long polyunsaturated acyl chains) and polar head groups (gangliosides, blycolipids) are typically present in the plasma membranes of excitable cells. The membrane-channel interactions will be explored by making small specific changes, for example by altering the charge or chemical composition of the polar head groups, by increasing unsaturation of the acyl chains or by exploring the effects of mixed lipids in the bilayer. It is reasoned that a quantitative analysis of the relationship between the internal and surface features of the supporting bilayer and those of the permeability pathway will reveal not only the functional role of membrane components in excitable membranes but also some of the basic mechanisms that underlie those pharmacological properties of excitable cell membranes (e.g., the effects of general anesthetics) which are mediated by structural changes of the bilayer-channel complex.